Autopsy Studies Turn Sudden Cardiac Death Wisdom on Its Head

New epidemiological research is challenging the long-held assumption that myocardial infarction is the primary cause of sudden cardiac death (SCD).

MI was the driver of sudden death in just 41% of cases of autopsy-confirmed SCD in a large US county, with the right coronary artery being the most common culprit vessel. Recently published in JACC, the findings throw cold water on conventional wisdom that approximately 80% of SCDs are due to MI, a misconception that goes back to the 1970s, say researchers.

“We have to acknowledge the new reality of sudden cardiac deaths, which is that 60% are not MI-related,” senior investigator Zian Tseng, MD (University of California, San Francisco), told TCTMD. “If we’re going to make strides in preventing sudden cardiac death, we need to shift to that reality.”

Investigators note that the annual incidence of SCD, ranging from 50 to 200 per 100,000 person-years, has remained high despite decades of advances in the treatment of coronary artery disease, including the use of primary-prevention implantable cardioverter-defibrillators (ICDs) for appropriate patients. The idea that SCD is largely attributable to MI stems from historical data, specifically a limited number of SCD cases referred for autopsy, that are open to referral bias, said Tseng.      

“We thought: let’s make sure that it’s still the underlying cause [of SCD],” he said. “If it’s not, we’re not directing our efforts in the right direction. We know that sudden cardiac death rates haven’t really declined very much, so are we really targeting the right thing anymore?”

In an editorial, Florence Dumas, MD, PhD, and Alain Cariou, MD, PhD (Paris Cité University, INSERM, France), praised the study, as well as a second JACC paper by the same group that found a high burden of undetected cardiac disease in SCD patients. Both studies are important for the epidemiology of SCD, they state, adding that the findings overturn established knowledge.

“Carried out in an unselected population, these results highlight that the actual proportion of SCD in which MI was considered [responsible] is much lower and that a substantial proportion are associated with nonobstructive coronary disease and disorders other than coronary disease, which leads to a different view of the epidemiology of SCD,” they write. “As a consequence, efforts should also be made to study the diagnosis and management of heart conditions other than ischemic cardiac disease.”  

POST SCD in San Francisco County

The World Health Organization’s widely adopted definition of SCD is a sudden, unexpected death within an hour of symptom onset (witnessed) or within 24 hours of last being seen alive (unwitnessed) in which a cardiac cause is assumed without autopsy. Several years back, the researchers showed that 40% of deaths attributed to SCD were not sudden or unexpected and roughly half of presumed SCDs were not the result of arrythmias.  

The new data, which were presented last week at Heart Rhythm 2026 and published in JACC, are based on continuous surveillance over a 12-year period in San Francisco County. The National Institutes of Health-funded POST SCD, as the project is known, is a partnership between cardiac electrophysiologists and the county medical examiner in which autopsy and medical history review is performed for all out-of-hospital cardiac arrest (OHCA) deaths.

Between 2011 and 2023, there were 943 presumed SCDs that underwent comprehensive postmortem examinations, and of these, 62% had autopsy-confirmed SCD and 38% were attributable to noncardiac causes. For the 583 autopsy-confirmed SCDs, 41% had histopathological evidence of acute or healed MI without other causes, leading to MI as the adjudicated cause of SCD. Of the 237 SCDs attributable to MI, 90% had evidence of CAD, with 95 identified as acute MI and 119 as healed MI. The remaining 10% of SCDs due to MI did not have evidence of CAD and were attributed to MI with nonobstructive coronary arteries (MINOCA).

“We not only looked at the autopsy, but we looked at the tissue for evidence of necrosis to define myocardial infarction. We didn’t rely on the coronary arteries, which is how we discovered that 10% of acute MIs were actually MINOCA. The coronaries were clean. So, if you only look at the coronary arteries, you’re going miss that,” Tseng said.

For the SCD cases attributable to acute MI with CAD, the right coronary artery was the culprit lesion in 43% of cases, the LAD in 36%, the left circumflex in 16%, and the left main in 6%.

“We were a little bit puzzled initially,” said Tseng. “Why is the right coronary artery the most common culprit artery? We then thought about the way we define sudden cardiac death and that there are survivors. People who make it to the cath lab, maybe they tend to have the LAD lesions? The ones that had RCA lesions don’t survive to get there. It’s sort of an analogy writ large for our study: we’re looking at things that never make it to clinical attention.”   

High Burden of Undetected Risk

In a second study, also presented at HRS and published in JACC, the POST SCD researchers found that a large proportion of arrhythmic SCD occurs in people without diagnosed cardiac disease.

Using the same data source of 943 presumed SCD cases, they identified 877 cases in which the individual had at least one healthcare visit. Of those, 58% had autopsy-confirmed SCD from arrhythmic causes, meaning they could have potentially been rescuable with an ICD or automated external defibrillator (AED).

For the 513 arrhythmic deaths, 32% of cases had documented clinical risk factors for SCD, such as LVEF ≤ 35%, heart failure, prior MI, or syncope. The remaining two-thirds of arrhythmic deaths occurred in people without documented risk factors. However, autopsy revealed that 31% of these people had occult MI or occult dilated cardiomyopathy. The remaining 36% of deaths attributable to arrhythmic causes, but without documented risk factors for SCD, showed signs of cardiac pathology, such as increased LV diameter or a higher burden of CAD when compared with trauma controls.

These results highlight that “there is a significant burden of undetected risk in the community,” said Tseng. “Two-thirds of people at risk for dying suddenly of arrhythmia have undetected severe disease, undetected risk factors, and so we need to do a better job in screening.”

With the data, Tseng said they have plans to study whether they can identify predictors of underlying pathology to find people at high risk for SCD. For example, patients in the early stages of dilated cardiomyopathy could be directed to heart failure specialists to ensure they are optimized on guideline-directed medical therapy (GDMT). Patients with a high burden of coronary artery disease could be treated with GDMT and/or referred for potential revascularization.

“It doesn’t necessarily mean everybody needs an ICD,” he said. “If we can more precisely target the underlying risk populations, we can potentially get them connected to earlier prevention.”

In their editorial, Dumas and Cariou state that the detection of patients at risk for SCD remains challenging. These new data showing that widely used markers of risk, such as occult MI, dilated cardiomyopathy, or other signs of cardiac pathology are missed in two-thirds of individuals dying suddenly from lethal arrhythmia challenge current prevention strategies, they say.

“By revealing that one-half of these silent arrhythmic deaths had occult MI or dilated cardiomyopathy detected by autopsy (whereas the remainder still had other cardiac diseases), they reaffirm the critical importance of improved detection of occult cardiovascular disease in preventing sudden death,” the editorialists conclude.